Supplementary Material

The Supplementary Material contains a proof that FBA-Gap is NP-Complete and tables related to computational results. A list of low-cost exchange reactions is in Table S1. Results from the first round of FBA-Gap for B. subtilis, T. cruzi, H. pylori, E. coli, and C. neoformans are in Table S2. For the C. neoformans model, the _rst step of FBA-Gap yields that the metabolites in Table S3 are an in_nite distance from the biomass reaction. The results of three rounds of gap analysis are in Tables S4-S7 below. Each table contains the transport reactions selected, and the action taken to avoid high-cost transports in the next round of gap analysis. In general, reactions are added only if they are in the MetModel GUI database and if KEGG specifies that a gene encodes the appropriate enzyme in the organism. The reactions in the final working model for C. neoformans is in Table S8. Table S9 contains reactions deleted from the B. subtilis model, and Table S10 contains the results of applying FBA-Gap to the broken model.